Repurposing Siponimod for Alzheimer's Disease

Summary

Collaboration with multiple sclerosis (MS) specialty colleagues led us to formulate the central hypothesis that Siponimod could lower the rate of brain atrophy in Alzheimer's disease (AD) subjects. To test our central hypothesis, we will carry out an 18-month Phase II, double-blind, randomized, twoarmed, placebo controlled, proof-of-concept clinical study in early AD subjects (i.e. mild AD) who will be receiving an escalating dose of Siponimod or placebo in the ratio 2:1 for 12 months, followed by a 6-month washout period. The primary outcome measures are safety and tolerability of Siponimod in mild AD subjects. The secondary outcome measures are the rates of brain atrophy derived from volumetric MRI (vMRI) as a proxy for neurodegeneration conducted at baseline, 6, 12, and 18 months. The tertiary outcome measures are the changes in cognition and the levels of AD-associated (e.g., Aβ and tau) and inflammatory biomarkers in CSF after Siponimod exposure. In an exploratory effort, we will also measure plasma inflammatory markers during the entire duration of the study to investigate whether one or more of these markers can be used as dynamic surrogate markers of treatment response. Using our unique experience with the repurposing of immunomodulatory drugs for AD (and NCT #04032626), in the present project we are using elements of clinical trial design that we believe were successful and made some adjustments to fit the pharmacologic and toxic properties of Siponimod.

Conditions

• Alzheimer Disease
• Mild Alzheimer Disease
• MCI With Increased Risk for Alzheimer Disease
• Cognitive Impairment, Mild

Interventions

DRUG

Siponimod

Siponimod (formerly known as BAF312 and completed trial NCT #01665144) has been FDA approved since 2019 (IND #076122) for the treatment of multiple sclerosis. Siponimod is an immunomodulator that prevents the egression of T lymphocytes from peripheral lymphoid organs.

DRUG

Placebo

A placebo that resembles siponimod will be given once daily to participants randomly assigned into the placebo arm.

Sponsors & Collaborators

• Texas Tech University Health Sciences Center

  collaborator OTHER

• Arizona State University

  collaborator OTHER

• National Institute on Aging (NIA)

  collaborator NIH

• Novartis

  collaborator INDUSTRY

• Laboratory Corporation of America

  collaborator INDUSTRY

• St. Joseph's Hospital and Medical Center, Phoenix

  lead OTHER

Principal Investigators

• Marwan N Sabbagh, MD · St. Josep's Hospital and Medical Center, Phoenix

• Boris Decourt, PhD · Texas Tech University Health Sciences Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

50 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-08-26

Primary Completion

2029-10-31

Completion

2029-10-31

FDA Drug

Yes

Countries

• United States

Study Locations